A Phase 3，Randomized，Open，Parallel Controlled, Multi-center Study of TQB2450 Injection Plus Chemotherapy Followed by TQB2450 Plus Anlotinib Versus Tislelizumab Plus Chemotherapy Followed by Tislelizumab as a First-line Treatment on Patient With Advanced Non-squamous NSCLC
Overview
- Phase
- Phase 3
- Intervention
- TQB2450 injection, Tilelizumab injection, Anlotinib hydrochloride capsule, Pemetrexed disodium injection, Carboplatin injection
- Conditions
- Advanced Non-squamous Non-small Cell Lung Cancer
- Sponsor
- Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
- Enrollment
- 390
- Locations
- 1
- Primary Endpoint
- Disease Control Rate (DCR）
- Last Updated
- 4 years ago
Overview
Brief Summary
This is Phase 3, randomized, open-label, parallel controlled study designed to compare the efficacy and safety of TQB2450 in combination with platinum-containing chemotherapy followed by TQB2450 plus Anlotinib versus tislelizumab in combination with platinum-containing chemotherapy followed by tislelizumab in locally advanced (stage ⅢB/ⅢC), metastatic or recurrent ( Stage IV) non-squamous NSCLC cancer. The primary endpoint is Progression Free Survival (PFS) assessed by IRC.
Investigators
Eligibility Criteria
Inclusion Criteria
- •1 According to the 8th edition of the International Association for the Study of Lung Cancer and the American Joint Committee on Cancer Classification, the TNM staging of lung cancer is locally advanced (stage ⅢB/ⅢC), metastatic or recurrent ( Stage IV) NSCLC patients.
- •2 Between the ages of 18-75 years (calculated based on the date of signing ICF); male or female; Eastern cooperative oncology group (ECOG) score 0-1; estimated survival time ≥ 3 months.
- •3 According to the RECIST 1.1 standard, there is at least one measurable lesion. If the measurable lesion is located in the radiotherapy area, it should be clearly defined as a progressive state.
- •4 Patients who have not received systemic anti-tumor therapy for advanced, recurrent or metastatic diseases in the past. For those who have received adjuvant chemotherapy in the past, the interval between the recurrence time and the last adjuvant chemotherapy should be at least 6 months; The interval between the end of previous radiotherapy for chest and this treatment should be more than 6 months, and the interval between palliative radiotherapy for chest and this treatment should be more than 7 days.
- •5 Tumor tissue sections that have not undergone radiotherapy at or after the diagnosis of advanced or metastatic NSCLC must be provided. Tumor tissue samples must be archived samples or freshly obtained samples within 12 months before randomization.
- •6 For non-squamous NSCLC, patients with no EGFR sensitive mutations, ALK fusion, ROS1 fusion
- •7 The function of main organs are well and meet the following standards:
- •8 a. Routine blood examination standards (without blood transfusion or correction with hematopoietic stimulating factor drugs within 14 days before screening): i. Absolute neutrophil count (ANC) ≥1.5×109 /L; ii. Platelets ≥100×109 /L; iii. Hemoglobin ≥90 g/L. b. The blood biochemical examination shall meet the following standards: i. Total bilirubin (TBIL) ≤ 2 × upper limit of normal (ULN) (Patients with Gilbert syndrome ≤ 3 × ULN); ii. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST)≤2.5×ULN. If it is accompanied by liver metastasis, ALT and AST≤5×ULN; 8.iii. Serum creatinine (Cr) ≤1.5×ULN or creatinine clearance estimated by Cockcroft-Gault glomerular filtration formula ≥60 mL/min; iv. Serum albumin (ALB) ≥30g/L. c. Urine routine examination standard: urine routine indicates urine protein \<++; if urine protein ≥++, it is necessary to confirm that the 24-hour urine protein quantitative ≤1.0 g.
- •d. Blood coagulation test standards: prothrombin time (PT), activated partial thromboplastin time (APTT), international normalized ratio (INR)≤1.5×ULN (no anticoagulant therapy).
- •e. Thyroid Stimulating Hormone (TSH) ≤ ULN; if abnormal, T3 and T4 levels should be examined. If T3 and T4 levels are normal, it can be selected.
Exclusion Criteria
- •1 Tumor disease and medical history:
- •Brain metastases without local treatment; Note: Subjects who have previously received brain metastasis therapy and meet all the following criteria can participate in this study: i. Only supratentorial and cerebellar metastases; ii. The condition needs to be stable for ≥4 weeks and no new brain metastases or brain metastases are found Expanded imaging evidence; iii. The subject must have stopped corticosteroids/dehydrator for at least 2 weeks before starting to use the trial drug;
- •There are midbrain, pons, medulla oblongata, spinal cord and meningeal metastases；
- •Other malignant tumors appeared or were present within 3 years. The following two cases can be included: other malignant tumors treated by single operation have achieved 5-year Disease-free survival (DFS) in a row; The cured cervical carcinoma in situ, non melanoma skin cancer and superficial bladder tumor \[ta (non-invasive tumor), tis (carcinoma in situ) and T1 (tumor infiltrating basement membrane)\];
- •Central type, cavity squamous cell carcinoma (primarily in the main bronchus and around the hilar);Imaging shows that the tumor invades large blood vessels or is unclearly separated from the blood vessels, or the investigator judges that the tumor is likely to invade important blood vessels and cause fatal bleeding during the subsequent study(The major vessels in the chest include pulmonary aorta, left pulmonary artery, right pulmonary artery, four pulmonary veins, superior vena cava, inferior vena cava and aorta);
- •Severe bone injury caused by tumor bone metastasis, including pathological fracture of weight-bearing bone and spinal cord compression that occurred within 6 months or is expected to occur in the near future(Such as spine, pelvis, femur, tibia, phalanges, calcaneus, etc.);
- •Patients with serous cavity (thoracic cavity, abdominal cavity, or pericardial cavity) that require repeated drainage to relieve clinical symptoms (as determined by the investigator), or who have received drainage of serous cavity effusion for the purpose of treatment within 2 weeks before treatment.
- •2 Previous anti-tumor treatments:
- •Received the treatment of proprietary Chinese medicines with anti-tumor indications specified in the NMPA approved drug instructions within 2 weeks before the start of the study treatment(Including compound cantharidin capsules, Kangai injection, Kanglaite capsule/injection, Aidi injection, brucea javanica oil injection/capsule, Xiaoaiping tablet/injection, Huachansu capsule, etc.);
- •Previously received related immunotherapy drugs for programmed death 1 (PD-1), PD-L1, cytolytic T lymphocyte-associated antigen-4 (CTLA-4), etc.;
Arms & Interventions
TQB2450 injection + carboplatin + pemetrexed
TQB2450 injection：1200 mg, Intravenous drip d1； carboplatin ：Area Under Curve 5mg/mL/min，Intravenous drip d1；Pemetrexed: 500mg/m2，Intravenous drip d1.The above schemes are repeated every three weeks. After 4 cycles, the regimen is changed to TQB2450 injection（1200 mg, Intravenous drip d1）+Pemetrexed（500mg/m2，Intravenous drip d1）+ Anlotinib (10mg, peros every day, d1-14) . The regimen is repeated every 3 weeks until the disease progresses.
Intervention: TQB2450 injection, Tilelizumab injection, Anlotinib hydrochloride capsule, Pemetrexed disodium injection, Carboplatin injection
TQB2450 injection + Anlotinib + Pemetrexed
Tilelizumab: 200 mg, Intravenous drip d1;carboplatin : AUC 5mg/mL/min, Intravenous drip d1；Pemetrexed: 500mg/m2, Intravenous drip d1.The above schemes are repeated every three weeks. After 4 cycles, the regimen is changed to Tilelizumab (200 mg, Intravenous drip d1)+Pemetrexed (500mg/m2，Intravenous drip d1).The regimen is repeated every 3 weeks until the disease progresses.
Intervention: TQB2450 injection, Tilelizumab injection, Anlotinib hydrochloride capsule, Pemetrexed disodium injection, Carboplatin injection
Outcomes
Primary Outcomes
Disease Control Rate (DCR）
Time Frame: Up to 2 years
Proportion of subjects whose tumors shrink or remain stable for a certain period, including CR, PR and stable disease SD
Progression Free Survival (PFS) assessed by IRC
Time Frame: Up to 2 years
The period from the first use of the drug to disease progression or death (whichever occurs first).
Duration of Remission (DOR)
Time Frame: Up to 2 years
The period from firstly-recorded objective tumor response (CR or PR) to firstly-recorded objective tumor progression or death due to any cause (whichever occurs first) .
Overall survival (OS)
Time Frame: Up to 3 years
Time from randomization to death
According to response evaluation criteria in solid tumours 1.1（RECIST1.1）standard and iRECIST （Immune-related response evaluation criteria in solid tumours ）standard researcher's assessment of progression-free survival (PFS)
Time Frame: Up to 2 years
The period from the first use of the drug to disease progression or death (whichever occurs first).
Objective Response Rate (ORR)
Time Frame: Up to 2 years
Proportion of patients whose tumor volume shrinks to a predetermined value and maintains the minimum time limit
TTR
Time Frame: Up to 2 years
Time from randomization to onset of remission (PR)
Secondary Outcomes
- Incidence and severity of adverse events (AEs) and serious adverse events (SAEs)，as well as abnormal laboratory examination indicators.(Up to 2 years)